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Combined effects of Notch signaling and cytokines induce a multiple log increase in precursors with lymphoid and myeloid reconstituting ability
Open accessAbstract
We investigated whether combined signaling induced by engineered Notch ligands and hematopoietic growth factors influences hematopoietic stem-cell differentiation. We show that incubation of murine marrow precursors with Delta1ext-IgG, a Notch ligand consisting of the Delta1 extracellular domain fused to the Fc portion of human immunoglobulin G1 (IgG1), and growth factors stem cell factor (SCF), interleukin 6 (IL-6), IL-11, and Flt3-l inhibited myeloid differentiation and promoted a several-log increase in the number of precursors capable of short-term lymphoid and myeloid repopulation. Addition of IL7 promoted early T-cell development, whereas addition of granulocyte-macrophage colony-stimulating factor (GM-CSF) led to terminal myeloid differentiation. These results support a role for combinatorial effects by Notch and cytokine-induced signaling pathways in regulating hematopoietic cell fate and suggest the usefulness of Notch ligand in increasing hematopoietic precursor numbers for clinical stem-cell transplantation.
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Cited by
Delaney, C., Heimfeld, S., Brashem-Stein, C., Voorhies, H., Manger, R. L., & Bernstein, I. D. (2010) · Nature Medicine · doi:10.1038/nm.2080 · Cited by 771
Self-citationNotch Signaling in the Immune System
Radtke, F., Fasnacht, N., & MacDonald, H. R. (2010) · Immunity · doi:10.1016/j.immuni.2010.01.004 · Cited by 543
Notch regulation of lymphocyte development and function
Radtke, F., Wilson, A., Mancini, S. J. C., & MacDonald, H. R. (2004) · Nature Immunology · doi:10.1038/ni1045 · Cited by 539
Hematopoietic stem cell fate is established by the Notch-Runx pathway
Burns, C. E., Traver, D., Mayhall, E., Shepard, J. L., & Zon, L. I. (2005) · Genes & Development · doi:10.1101/gad.1337005 · Cited by 401
Signaling pathways governing stem-cell fate
Blank, U., Karlsson, G., & Karlsson, S. (2008) · Blood · doi:10.1182/blood-2007-07-075168 · Cited by 355
Metadata
- Authors
- Varnum-Finney, B., Brashem-Stein, C., & Bernstein, I. D.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2003-03-01
- Volume
- 101
- Issue
- 5
- Pages
- 1784-1789
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2051292725
- Cited by
- 267
- References
- 0
- FWCI
- 10.09
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Varnum-Finney, B., Brashem-Stein, C., & Bernstein, I. D. (2003). Combined effects of Notch signaling and cytokines induce a multiple log increase in precursors with lymphoid and myeloid reconstituting ability. Blood. https://doi.org/10.1182/blood-2002-06-1862
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